title: Transgene- and locus-dependent imprinting reveals allele-specific chromosome conformations.
abstract: When positioned into the integrin α-6 gene, an Hoxd9lacZ reporter transgene displayed parental imprinting in mouse embryos. While the expression from the paternal allele was comparable with patterns seen for the same transgene when present at the neighboring HoxD locus, almost no signal was scored at this integration site when the transgene was inherited from the mother, although the Itga6 locus itself is not imprinted. The transgene exhibited maternal allele-specific DNA hypermethylation acquired during oogenesis, and its expression silencing was reversible on passage through the male germ line. Histone modifications also corresponded to profiles described at known imprinted loci. Chromosome conformation analyses revealed distinct chromatin microarchitectures, with a more compact structure characterizing the maternally inherited repressed allele. Such genetic analyses of well-characterized transgene insertions associated with a de novo-induced parental imprint may help us understand the molecular determinants of imprinting.
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lonfat
authors.forename: Thomas
authors.initials: T
authors.lastname: Montavon
authors.forename: David
authors.initials: D
authors.lastname: Jebb
authors.forename: Patrick
authors.initials: P
authors.lastname: Tschopp
authors.forename: Thi Hanh
authors.initials: TH
authors.lastname: Nguyen Huynh
authors.forename: Jozsef
authors.initials: J
authors.lastname: Zakany
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics* / Q000648:ultrastructure; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D017403:In Situ Hybridization; D039503:Integrin alpha6 / Q000235:genetics*; D007763:Lac Operon / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019076:Transgenes / Q000235:genetics*; D001616:beta-Galactosidase
chemical_list: D002843:Chromatin; D017931:DNA Primers; D039503:Integrin alpha6; D001616:beta-Galactosidase
keywords: Hox genes; architecture; enhancer; epigenetic